Nanolithography has been recognized as essential to future technologies. Many currently existing lithographic techniques, however, have significant limitations in terms of resolution, writing speed, and the chemical diversity of the materials that can be patterned on a particular substrate. Lithographic techniques employing scanning probe microscopy (SPM) have become increasingly popular due to their potential application in low-cost and/or parallelized fabrication of nanoscale structures. For the most part, SPM-based techniques have been used for direct writing of nanostructures through indentation or through material deposition and/or removal, as well as for normal resist exposures as masks for other lithographic processes. By way of example, dip-pen nanolithography (DPN) offers several interesting capabilities, but requires stringent control over the environment/atmosphere and has limitations in substrate choice, patterning speed, and topographical change control.
Recently it has been demonstrated that SPM tips can act as mechanical, thermal, and/or electrical sources to initiate and perform various physical and chemical processes. These tips are inherently simple and reliable, and have the flexibility to create patterns with nanoscale spatial resolution. In fact, such techniques are capable of creating topographical nanopatterns with a spatial resolution on the order of about 10 nanometers (nm). In contrast, achieving chemical patterning, even at resolutions of less than or equal to about 100 nm, still remains a challenge because of the difficulty in spatially confining chemical reactions and because of the need to control the interactions of the reactant and products with the substrates and, if necessary, stamps. By extension, combining the two concepts (i.e., topographical and chemical nanopatterning) has been even more challenging.
There accordingly remains a need in the art for improved lithographic techniques. Significant new opportunities could open up with the development of these improved techniques. The biotechnology arena provides just one illustration of such opportunities. At the forefront of nanobiotechnology is the challenge to manipulate and control the surface positioning of individual proteins, nanoparticles, and other complex nanostructures. Achieving this aim could facilitate the development of protein chips with single molecule detection capability, nanoelectronics devices, and to assist in fundamental studies of complex cell-cell and cell-matrix interactions (e.g., formation of immunological synapses, focal contacts, and the like).
While advances have been made in patterning inorganic nanoscale objects, challenges still exist, in particular, for protein and DNA nanolithography. Many protein nanopatterning techniques are unable to produce features below 100 nm, and even fewer can attain resolutions on the order of about 50 nm. In addition, only a few protein nanopatterning techniques have been established for independently patterning multiple protein species on the same surface. Still further, bioactivity is a particularly delicate problem because denaturation, oxidation, and dehydration in air are common drawbacks that complicate many potential protein nanopatterning techniques. These considerations also limit the choice of surfaces onto which the proteins can be patterned. For example, proteins directly chemisorbed onto gold tend to denature.
Thus, new protein or DNA nanopatterning techniques should strive to obtain resolutions below 50 nm, achieve high writing speeds, reduce costs, produce multiple functionalities that can coexist on a single surface, preserve biological functionality, and be compatible with a variety of substrates.